Blackberry, raspberry and black raspberry polyphenol extracts attenuate angiotensin II-induced senescence in vascular smooth muscle cells

Abstract

Activation of angiotensin II (Ang II) signaling during aging increases reactive oxygen species (ROS) leading to vascular senescence, a process linked to the onset and progression of cardiovascular diseases (CVD). Consumption of fruits and vegetables, particularly berries, is associated with decreased incidence of CVD, which has mainly been attributed to the polyphenol content of these foods. Thus, the objective of this study was to investigate the role of blackberry (BL), raspberry (RB), and black raspberry (BRB) polyphenol extracts in attenuating Ang II-induced senescence in vascular smooth muscle cells (VSMCs) and to determine the molecular mechanisms involved. BL, RB and BRB polyphenol extracts (200 μg ml) attenuated Ang II-induced senescence, denoted by decreased number of cells positive for senescence associated β-galactosidase (SA-β-gal) and down-regulation of p21 and p53 expression, which were associated with decreased ROS levels and Ang II signaling. BL polyphenol extract increased superoxide dismutase (SOD) 1 expression, attenuated the up-regulation of Nox1 expression and the phosphorylation of Akt, p38MAPK and ERK1/2 induced by Ang II, and reduced senescence in response to Nox1 overexpression. In contrast, RB and BRB polyphenol extracts up-regulated the expression of SOD1, SOD2, and glutathione peroxidase 1 (GPx1), but exerted no effect on Nox1 expression nor on senescence induced by Nox1 overexpression. BRB reduced signaling similar to BL, while RB was unable to reduce Akt phosphorylation. Furthermore, we demonstrated that inhibition of Akt, p38MAPK and ERK1/2 as well as down-regulation of Nox1 by siRNA prevented senescence induced by Ang II. Our findings indicate that Ang II-induced senescence is attenuated by BL polyphenols through a Nox1-dependent mechanism and by RB and BRB polyphenols in a Nox1-independent manner, likely by increasing the cellular antioxidant capacity.

Duck Oil-loaded Nanoemulsion Inhibits Senescence of Angiotensin II-treated Vascular Smooth Muscle Cells by Upregulating SIRT1

“…Recently, Ang II was reported to trigger aging of vascular smooth muscle cells (VSMCs) by ARTICLE causing oxidative DNA damage which is intimately linked to the stability of atherosclerotic plaques (Herbert et al, 2008;Matthews et al, 2006). These findings are consistent with the reports that blockade of Ang II activity by polyphenols, such as resveratrol and those found in berries, inhibits vascular senescence-mediated intracellular signaling, leading to blockade of vascular age-associated diseases including atherosclerosis (Feresin et al, 2016;Kim et al, 2018;Najjar et al, 2005). Thus, aging-related vascular disorders may be prevented by controlling cellular senescence.…”

NADPH Oxidases and Mitochondria in Vascular Senescence

“…The kinases p38MAPK, Akt, and extracellular signal-regulated kinase (ERK)1/2 mediate Ang II-induced effects in VSMCs [ 44 , 45 ]. We previously reported that inhibition of any of these kinases reduced senescence induced by Ang II in VSMCs [ 46 ], suggesting that Ang II-induced senescence is complex, and could be mediated by multiple mechanisms. Some of the molecular mechanisms regulating Ang II-induced senescence reported by us and others are summarized in Figure 2 .…”

Transcriptomics, Targeted Metabolomics and Gene Expression of Blackberry Leaves and Fruits Indicate Flavonoid Metabolic Flux from Leaf to Red Fruit

“…These molecules have been reported to have beneficial effects to prevent metabolic syndrome at different levels such as cardiovascular disease and type II diabetes; hence, including blackberry on human diet is beneficial for health (Tavares et al, 2013; Feresin et al, 2016; Sarkar et al, 2016). On the other hand, they play a relevant role in plant defense against biotic and abiotic stress (Daayf et al, 2012).…”